Dementia refers to a group of disorders characterized by progressive loss of cognitive functions. It is more than forgetting or age related changes in memory. A cascade of events has to occur in the brain for dementia to be evidenced in behavior.

Some dementia is temporary. Irreversible dementia can be divided into four categories of origin: degenerative diseases; vascular diseases; traumatic dementia and infections. Alzheimerís disease, Lewy body dementia and vascular dementia account for most cases of dementia (See below for a full list of diseases that may cause dementia.) Progression of the dementia associated with these diseases invariably leads to increasing dependence on others for everyday care as well as increasing health costs. Medicare, except in extraordinary circumstances, does not pay for long term custodial care for dementia.(See Medicare articles). Residents of nursing homes usually have to spend down their savings before being covered by Medicaid.

In its initial stage, dementia is characterized by some degree and quality of change in behavior and cognition, and not by any presence of specific histological changes that are measurable. It is hard to diagnose in this initial phase. To date, there are no biological tests for dementia itself. In many cases, those around the patient are aware of subtle changes in behavior and memory. Sometimes the individual is aware of cognitive changes, but does not attribute it to dementia. At the same time, individuals worry about "forgetting" and have anxious moments filled with thoughts about becoming demented. An individual's anxiety over this issue can be debilitating in of itself. Neuropsychological tests may pick up early signs of possible dementia before they express themselves.

Psychotic features associated with dementia involve altered perceptions, which may include hallucinations, misperceptions and delusions. Hallucinations, when present, are most commonly visual (actually see things that are not there as opposed to thought broadcasting or thought insertion). Typical misperceptions include inability to recognize oneself in a mirror and an inability to distinguish a real person from a TV image. Delusions are most commonly paranoid and relate to the ideas of theft, abandonment or infidelity.

The clinical features of dementia often point to a specific cause. In patients with Alzheimerís disease, memory loss, language impairment and visuospatial disturbances (distance as well as place is misjudged; also not sure where they are) are typical. Often these patients appear indifferent and experience delusions and agitation especially during advanced stages.

Frontotemporal dementia e.g. Pickís disease, by contrast, evidences marked personality changes and executive dysfunction (difficulty in higher order capabilities that are called upon in order to formulate new plans of action and to select, schedule and monitor appropriate sequence of action) but a relative preservation of visuospatial skills.

Patients with dementia called Lewy body type display symptoms such as tremors, stiffness, or some signs of Parkinson disease. They may experience visual hallucinations, delusions, fluctuating mental status and evidence a high degree of sensitivity to neuroleptic medications.

The depression symptoms associated with Alzheimer's disease tend to be indirect, taking the form of agitation and insomnia. This contrasts with depression as a primary diagnosis, where the patient exaggerates cognitive deficits and appears poorly motivated. Such patients also emphasize mood complaints, while language and motor skills remain in tact. Here is where diagnosis proves important. Specialists is geriatric medicine should be consulted along with a neuropsychological evaluation to distinguish depression from Alzheimerís Disease.

VASCULAR DEMENTIA

The main focus of therapy in vascular dementia is prevention. It has been argued that once a patient fulfills the criterion for dementia, it is too late to do anything. Improved control of hypertension and cessation of smoking reduce the risk of developing vascular dementia.

Determining the prevalence of vascular dementia is problematic. Lack of agreement on the definition of this disorder has resulted in widely varying prevalence rates. One problem is that vascular dementia is a syndrome with multiple causes and multiple manifestations. There is a great deal of controversy regarding the relationship between vascular brain injury and dementia. It is unclear what size, type and the number of lesions, and in what location, will cause dementia. Many vascular lesions have been seen using computerized tomography (CT) or magnetic resonance imagery (MRI) in people with normal cognition.

Is vascular dementia primarily a dementia, or a vascular disease, which can be treated? Is it a consequence or a special form of cerebrovascular disease, or do patientís who are going to develop it need to have some additional degenerative changes in order to become demented? These are things that are not very clear at this time.

The diagnosis of vascular dementia depends on the criteria selected and on the presumed pathophysiology and symptoms that can be detected and recognized in a particular patient. If a patient is demented, and if there are clear signs and symptoms of cerebrovascular disease (stroke), and if the dementia follows shortly after the cerebrovascular events, the diagnosis of vascular dementia is probably clear.

ALZHEIMERíS DISEASE

Alzheimerís disease causes a devastating loss of cognitive and functional capacities. It is estimated that more than 4 million people in the US currently suffer from AD. At some point in time virtually all persons with AD will require continuous care. The psychological and financial burdens are devastating to everyone involved with an AD patient.

In many ways, taking care of patients with AD is different from assisting patients with only physical ailments. For example, patients with AD have impaired insight, often misjudging or denying the extent of their physical and mental impairment. These patients may perceive the intervention of a caregiver who assists them with performing the activities of daily life (ADL) as an indignity and, mistakenly, as an imposition. Consequently, patients with AD frequently display behaviors that are disturbing to the caregiver and disruptive to the caregiving process. These include resistance, rejection, agitation, negativism, and verbal or physical aggressiveness and abuse. These behavioral changes are, at least in part, accompanied by changes in neuromotor function. With the progression of the disease, the brain is increasingly less capable of selecting and modifying its responses to various incoming stimuli. Consequently, the body of a patient with AD reacts differently to a variety of external stimuli that act upon it compared to the body of a healthy person. These fundamental changes in neuromotor function profoundly complicate patient care because they limit the patientís physical capability to cooperate with the caregiver.

AD is characterized in the brain by the deposition of amyloid protein outside the neuron, resulting in the formation of plaques and inside the neuron with neurofibrillary tangles, which are cytoskeletal components that affect the way the neuron functions. The number of synapses is decreased in AD. The synapse is the unit of communication between cells. Loss of synapses is reflected in dementia. This loss occurs across a number of different kinds of neurons that make different kinds of neurotransmitters, but not in all areas of the brain or across all neurons. They are most seen in temporal and parietal regions with extension to frontal cortex of the brain. The neurotransmitters, which are most often affected, are those known to be involved in the learning and memory processes. Acetylcholine is eventually diminished in virtually all patients with AD. There is a deficiency in CSF immunoreactivity and somatostatin immunoreactivity. The assumption made is that the cells that make these neuropeptides are dysfunctional and are losing synapses as well.

Diagnosis is generated by a history of progressive deterioration over some period of time in at least two domains of cognition, of which one is usually memory. Apolipoprotein E genotyping is not considered diagnostic for AD. In 5% of all the Alzheimerís disease cases, a chromosome deficiency has been found. This is called early-onset Alzheimerís disease and manifests itself before the age of 65. The vast majority of AD appears to be sporadic and involve a process not fully understood to date, with the amyloid precursor protein playing some important role. (See below.)

Non-cognitive symptoms associated with AD, such as agitation, paranoia, uncooperativeness and depression can be treated. This makes for a better quality of life for the patient, though it is not a cure for Alzheimerís disease. Psychoactive agents with anticholinergic effects and benzodiazepines should not be used because they can worsen cognition. (See our series of articles on AD listed below).

A number of potential therapies are currently under investigation including estrogen replacement, anti-inflammatory agents, free radical scavengers and antioxidants, and monoamine oxidase-B9 (MAO-B) inhibitors. (For a list of drug companies doing research in this area see articles under Alzheimerís disease on this web site) In addition, other approaches, such as anti-amyloid treatments that affect beta-amylase secretion, aggregation and toxicity, appear promising; treatments that hinder neurofibrillary tangle construction and nerve growth factor (NGF) induction are in the early stages of development.

In AD, progressive loss of cognitive abilities usually begins with difficulties in episodic memory (refers to the ability to remember personally experienced events such as what you had for breakfast the previous day) and soon encompassing language, visuospatial and executive dysfunction. The classical pathological features include neurofibrillary tangles, amyloid plaques and neuronal and synaptic loss.

Risk factors for developing AD include advancing age, family history of dementia, substandard education, a history of head injury and a history of smoking. Lower risk has been reported with a history of arthritis, use of NSAIDís and use of estrogen replacement in postmenopausal women.

Researchers are still trying to understand the disease process. Three genes have been identified; beta amyloid precursor protein (b -APP) and two presenilin proteins (PS1 & PS2) that cause early-onset AD (before 65 years), whereas apolipoprotein E (ApoE) epsilon 4 has been identified as a susceptibility gene for late onset disease. Other events have to occur for it to evidence penetration (Swartz RH, Black SE, St. George-Hyslop P. Apolipoprotein E and AD: a genetic, molecular and neuroimagery review. Canadian Journal of Neurological Sciences 1999; 26:77-88)

LEWY BODIES

Lewy bodies are found in the substantia nigra of patientís with Parkinsonís disease (in the neocortex, limbic structures, and brain stem of patients with Parkinsonís disease and dementia). They are also found in association with the neuropathologic features of Alzheimerís disease in the neocortex, limbic structures and brain stem of patients with dementia and varying features of Parkinsonís disease referred to as the Lewy body variant of Alzheimerís disease.

The clinical criteria for diagnosis of Lewy body type are:

(A) fluctuating cognitive impairment;
(B) at least one of the following: visual or auditory hallucinations usually accompanied by delusions; mild extrapyramidal side effects of sensitivity to neuroleptic drugs; or repeated unexplained falls, transient clouding, or loss of consciousness;
(C) rapid progression to severe dementia compared to the clinical finding of Alzheimerís disease.

The lower cerebral spinal fluid levels of homovanillic acid were significant in the Lewy body patients. This reduced metabolism of dopamine may be related in part to the presence of the Lewy bodies in the mesolimbic and mesocortical areas, and may correlate to the higher frequency of psychotic symptoms.

Features which distinguish dementia from pseudodementia due to depression

Dementia

Pseudodementia due to depression

Long term Course

Short Term course

Cognitive loss consistent

Cognitive loss variable and selective

Few "donít know" answers

Many "donít know" answers

Delusions unusual and consistent

Negative delusions common and persistent

Hallucinations rare

Auditory hallucinations quite common

Emotional responses few and variable

Often sad and distressed

No response to a trial of antidepressants

Responds to antidepressant therapy

Readers should be aware that there are many different medical causes of irreversible dementia. The following list is presented for your information. It is by no means an inclusive nor a definitive list of irreversible causes of dementia. In some cases, a drug regimen may retard the progress of the dementia or drugs may be developed in the foreseeable future to reverse the dementia process or prevent its occurrence. In all situations, we recommend that the treating physician be consulted and asked about available medications or herbal supplements, vitamins, minerals etc. that may retard the progress of the memory losses.

Delirium is defined as an acquired syndrome of impaired attention, alertness and perception. Delirious patients typically have a shortened digit span, while patients with Alzheimerís have a normal digit span until late in the disease. Memory functions in the delirious patient are characterized by registration impairment, while AD patients show impaired recall and recognition. Delirious patients also typically experience hallucinations and illusions, which are less common in AD. The onset of the two conditions generally differ-AD has a gradual onset, while delirium is usually more abrupt in onset.

The diagnosis of delirium is not well defined, but accumulated data indicates that the disorder might be due to disturbed cholinergic function in the brain. In dementia, where we know that cholinergic activity in the brain is reduced, the risk of developing delirium is increased. It is also clear that in the elderly, confusion is a common complication of the use of medications with anticholinergic effects.

Regarding the course of delirium, it is important to separate risk factors from precipitating factors. Aging, dementia and other degenerating neuropsychiatric disorders increase the risk of delirium, whereas somatic disorders usually precipitate confusion.

Delirium is assumed to be of short duration. However, thorough investigations of elderly patients indicate that there are also recurrent and chronic forms of delirium. Patients often show symptoms of restlessness and even aggression. These symptoms are controlled with powerful drugs such as neuroleptics to which elderly people are susceptible. The treatment is intended to make elderly patients easy to nurse rather than to improve their mental status.

Researchers have found that 35% of patients aged 65 years or older had delirium on admission or developed it during index hospitalization. In a geriatric setting, in an acute geriatric ward, OíKeefe and Laven found delirium was present in 18% of patients on admission and was developed in a further 24% of patients after admission.

Incidence of delirium after cardiac surgery, in a review by Smith and Dimsdale, indicated the incidence at 30%. In orthopedic surgery, the figures are much higher than general surgery, ranging from 25% to 50%. Hip surgery incidence of post delirium varied from 44% to 52% when patients with dementia were excluded. Figures in nursing homes indicate delirium in 44% of the population, with 43% of these patients also having dementia.

There are three subcategories of delirium: hyperactive, hypoactive and mixed delirium. In hyperactive the following symptoms appear: paranoia, hallucinations and illusions with symptoms worse in PM, evening and night. Those with morning delirium had a significantly higher incidence of stroke and heart disease than patients with a different diurnal variation.

Dementia remains a serious problem for our society to deal with and is a challenge to the scientific community to develop treatment protocols and preventive steps to insure higher quality of life to individuals as they age. The scientific community is putting great effort into this area, with new insights developing each day. Alzheimerís disease can become more manageable with proper treatment, but still is devastating to the individual and family. Hopefully, time will bring the answer.

For those readers interested in further exploring this area, we are supplying a bibliography of articles and books used in developing this series of web site articles. As we come across new articles, wee will add to this bibliography.

Filip, Vaclav & Kolbas, Eduard. Selegeline in the treatment of AD: a long-term randomized placebo-controlled trial. J Psychiatry Neuroscience 1999; 24(3): 234-243. ("Selegiline has a long-term beneficial effect in AD on memory modalities that reflect the function of the prefrontal areas of the brain, which are rich in dopamine receptors. The delayed appearance of differences between selegiline and placebo support the notion that the mechanism of action is through neuronal rescue or neuroprotection. The differential response of patients with normal and pathological results of the Clock Drawing Test may reflect the fact that evaluation methodsí sensitivity to change depends on the severity of dementia." Selegiline (also known as l-deprenyl) is an irreversible inhibitor of MAO-B. In humans, it is specific for type B MAO in dosages of less than 10 mg per day. In addition, selegiline may act as an antioxidant in neurons and protect against glutamate-receptor-mediated toxicity. Long term treatment in comparisonwith placebo improves cognitive and behavioral functions in patients suffering from mild to moderate AD.

Haan, Mary (1999). The role of APOE e 4 in modulating effects of other risk factors for cognitive decline in elderly persons. JAMA 1999; 282(1).

Perry Richard J., Hodges John. Attention and executive deficits in AD: A critical review. Brain 1999;122:383-404. (Executive functioning refers to the mental activity that is involved in planning, initiation and regulation of behavior.)

Pitchumoni, Suresh, BS & P. Murali Doraiswamy. Current status of antioxidant therapy in Alzheimerís disease. J Amer Geriatric Society 1998; 46:1566-1572. (Conclude "Preclinical evidence suggests a valuable role for antioxidant treatment to protect against free radical inducedneuronal death. Although this has not been confirmed in clinical trials, available clinical trial data is promising and supports continuing investigation. If oxidants such as vitamin E and gingko biloba are proven efficacious in additional AD trials, the simplicity of treatment ease of access and low cost render these agents highly attractive as treatment options to delay or slow the manifestation of this devastating disorder.")

Shua-Haim JR, Ross JS. Current and near future medications for AD: What can we expect from them. J of AD 1999;14(5):294-307.

Swartz RH, Black SE, St. George-Hyslop P. Apolipoprotein E and AD: A genetic, molecular and neuroimaging review. Canadian Journal of Neurological Science 199;26:77-88. (AD characterized by a progressive loss of cognitive abilities, usually beginning with difficulties in episodic memories and soon encompassing language, visuospatial and executive dysfunction. Classical pathological features include neurofibrillary tangles, amyloid plaques and neuronal and synaptic loss.)

Memory/Cognitive Decline

Salthouse TA. Initiating the formalization of theories of cognitive aging. Psychology & Aging 1988; 3:3-16. (Working memory, that allows one to hold an information while processing others, has been shown to be less efficient with aging.)

Haan, Mary. The role of APOE e 4 in Modulating Effects of other Risk Factors for Cognitive Decline in elderly persons. JAMA 1999; 282(1)